Development of a Selective Tumor-Targeted Drug Delivery System: Hydroxypropyl-Acrylamide Polymer-Conjugated Pirarubicin (P-THP) for Pediatric Solid Tumors

Makimoto, Atsushi; Fang, Jun; Maeda, Hiroshi

doi:10.3390/cancers13153698

Cited by 6 publications

(4 citation statements)

References 58 publications

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“…Although chemotherapies including DXR have been administered for unresectable low-risk NB in previous studies [2,23], chemotherapy that includes THP may be more beneficial to patients because of its superior antitumor efficacy and lower cardiotoxicity. In addition, an improved drug, hydroxypropyl-acrylamide polymerconjugated THP (P-THP), is being developed [24]. Thus, simply replacing other ACs with THP or P-THP in a regimen may improve outcomes in AC-sensitive pediatric cancers.…”

Section: Discussionmentioning

confidence: 99%

Pirarubicin Combination Low-Dose Chemotherapy for Early Infantile Stage MS Neuroblastoma: Case Report

et al. 2023

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Neuroblastoma (NB) is a neural crest-derived malignant tumor which is diagnosed during infancy in approximately 40% of cases; spontaneous regressions are observed, but there are varying degrees of severity. Treatment is indicated if an infant’s condition is at risk of deterioration. Herein, we report the case of a 42-day-old boy who presented with hepatomegaly and was diagnosed with stage MS NB. A pathological diagnosis of “poorly differentiated neuroblastoma with low mitosis-karyorrhexis index, favorable histology” was made; his tumor cells were hyperdiploid and MYCN was not amplified. Because he had respiratory distress caused by the rapidly evolving hepatomegaly, two cycles of chemotherapy containing vincristine and cyclophosphamide were administered in the second and fourth weeks of admission; however, his abdominal tumor did not shrink. In the sixth week of admission, chemotherapy was revised to pirarubicin and cyclophosphamide, and the tumor began to shrink. After discharge, there was no re-elevation of tumor markers; after 1 year, the hepatomegaly and liver metastases disappeared. During the 5-year follow-up, his growth and development were normal and he progressed without sequelae. A regimen that includes pirarubicin could merit further study in the treatment of early infants with stage MS low-risk NB who are at risk of complications.

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Section: Discussionmentioning

confidence: 99%

Pirarubicin Combination Low-Dose Chemotherapy for Early Infantile Stage MS Neuroblastoma: Case Report

et al. 2023

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“…The following table summarizes the list of approaches and methods of detection and their pros and cons for targeting cerebrospinal fluid for the discovery of brain cancer biomarkers: Highly specific [5][6][7] False negatives are common due to low sensitivity. [3,[15][16][17]…”

Section: Existing Workmentioning

confidence: 99%

“…Minimal differential power has been reported between mitosis and neoplastic cells. [16] Other tools: DNA cell measurement or fluorescent hybridization technique onsite to measure cancer cell chromosome content in cerebrospinal fluid It is possible to detect malignant localization from genetic aberrations detected by these technologies. [19] Low sensitivity [20] Detection of biochemical molecules secreted by cancer for CSF…”

Section: Detection Of Cancer Cells In the Csfmentioning

confidence: 99%

A Systematic Mapping Study of detection of Tumor Cell Targeted by Enzymes though Cerebrospinal Fluid

Saeed¹,

Abbasi²,

Hashim³

2023

Clin Cancer Investig J

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Cancers, especially of the neural tissue, are often deemed a death sentence. There is, however, still no clear understanding of the underlying causes nor the cellular and molecular mechanisms of this disease. The spread and collateral damage caused by various types of brain tumors remain poorly understood, despite the information that is currently available about these diseases. A common means of diagnosing tumors is through cerebrospinal fluid (CSF) leakage, and the enzymes from brain cancer cases were investigated within this hypothesis. The purpose of this study was to investigate the role of CSF in brain cancer and BBB. This study conducted a systematic study of leakage that typically occurs at the spine level, namely in the thoracic spine region and the base of the brain along the cardiothoracic connection. This study investigated the bacteria sampling of brain cancer in CSF and determined the common method of targeting cancer cells in the brain and enzymes contained within the CSF. A further finding reveals the precise foci of this leakage and various proteins and enzymes that may be responsible for this damage, as well as evidence that the release of tumor components damages the CSF. As a result of these observations, enzymes and tumor cells are detected, and a new component identifies tumor-related CSF.

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“…Pirarubicin (THP; Figure 1A) is a bladder perfusion drug recommended by the guidelines of NMIBC and commonly used in clinical practice, with a usual dose of 30-50 mg. THP is a new generation of synthetic anthracycline anti-tumor drugs. It plays an antitumor role by inhibiting DNA polymerase to interfere with the synthesis of DNA in cells, causing cell cycle arrest, and promoting tumor cell apoptosis [8]. The chemical structure of THP has another pyran ring on the basis of doxorubicin.…”

Section: Introductionmentioning

confidence: 99%

Genome-Wide Screening Identifies Gene AKR1C1 Critical for Resistance to Pirarubicin in Bladder Cancer

Nie

Gao

Chen

et al. 2023

Cancers

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Non-muscle-invasive bladder cancer (NMIBC) is a common tumor of the urinary system. Given its high rates of recurrence, progression, and drug resistance, NMIBC seriously affects the quality of life and limits the survival time of patients. Pirarubicin (THP) is a bladder infusion chemotherapy drug recommended by the guidelines for NMIBC. Although the widespread use of THP reduces the recurrence rate of NMIBC, 10–50% of patients still suffer from tumor recurrence, which is closely related to tumor resistance to chemotherapy drugs. This study was performed to screen the critical genes causing THP resistance in bladder cancer cell lines by using the CRISPR/dCas9-SAM system. Thus, AKR1C1 was screened. Results showed that the high expression of AKR1C1 could enhance the drug resistance of bladder cancer to THP both in vivo and in vitro. This gene could reduce the levels of 4-hydroxynonenal and reactive oxygen species (ROS) and resist THP-induced apoptosis. However, AKR1C1 did not affect the proliferation, invasion, or migration of the bladder cancer cells. Aspirin, which is an AKR1C1 inhibitor, could help reduce the drug resistance caused by AKR1C1. After receiving THP treatment, the bladder cancer cell lines could upregulate the expression of the AKR1C1 gene through the ROS/KEAP1/NRF2 pathway, leading to resistance to THP treatment. Using tempol, which is an inhibitor of ROS, could prevent the upregulation of AKR1C1 expression.

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Development of a Selective Tumor-Targeted Drug Delivery System: Hydroxypropyl-Acrylamide Polymer-Conjugated Pirarubicin (P-THP) for Pediatric Solid Tumors

Cited by 6 publications

References 58 publications

Pirarubicin Combination Low-Dose Chemotherapy for Early Infantile Stage MS Neuroblastoma: Case Report

Pirarubicin Combination Low-Dose Chemotherapy for Early Infantile Stage MS Neuroblastoma: Case Report

A Systematic Mapping Study of detection of Tumor Cell Targeted by Enzymes though Cerebrospinal Fluid

Genome-Wide Screening Identifies Gene AKR1C1 Critical for Resistance to Pirarubicin in Bladder Cancer

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